抗猫 TNF-α单克隆抗体的制备、鉴定及其在猫传染性腹膜炎治疗中的应用潜力。

Generation, characterization and therapeutic potential of anti-feline TNF-alpha MAbs for feline infectious peritonitis.

机构信息

Laboratory of Veterinary Infectious Disease, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan.

出版信息

Res Vet Sci. 2013 Dec;95(3):1248-54. doi: 10.1016/j.rvsc.2013.09.005. Epub 2013 Sep 19.

Feline infectious peritonitis (FIP) is a lethal infectious disease affecting domestic and wild cats. Several reports suggested that TNF-alpha is related to the progression of FIP. Thus, the administration of a feline TNF-alpha-neutralizing antibody to cats with FIP may reduce the disease progression. In this study, we have prepared nine monoclonal antibodies (MAbs) that recognize feline TNF-alpha. All MAbs neutralized recombinant TNF-alpha. The 50% inhibitory concentrations (IC50) of the MAbs for the cytotoxicity of recombinant TNF-alpha were 5-684 ng/ml. MAb 2-4 exhibited high neutralizing activity against natural TNF-alpha derived from FIPV-infected macrophages, and was confirmed to inhibit the following feline TNF-alpha-induced conditions in vitro: (i) an increase in the survival rate of neutrophils from cats with FIP, (ii) aminopeptidase N (APN) mRNA expression in macrophages, and (iii) apoptosis of a feline T-lymphocyte cell line.

猫传染性腹膜炎（FIP）是一种致命的传染病，影响家猫和野猫。有几项报告表明 TNF-α 与 FIP 的进展有关。因此，向患有 FIP 的猫施用猫 TNF-α 中和抗体可能会减缓疾病进展。在这项研究中，我们制备了九种识别猫 TNF-α 的单克隆抗体（MAb）。所有 MAb 均中和重组 TNF-α。MAb 的 50%抑制浓度（IC50）对于重组 TNF-α的细胞毒性为 5-684ng/ml。MAb 2-4 对源自 FIPV 感染的巨噬细胞的天然 TNF-α具有高中和活性，并被证实可抑制以下体外猫 TNF-α诱导的条件：（i）FIP 猫中性粒细胞存活率增加，（ii）巨噬细胞中氨肽酶 N（APN）mRNA 表达，以及（iii）猫 T 淋巴细胞系的凋亡。